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Elevated FBXL18 promotes RPS15A ubiquitination and SMAD3 activation to drive HCC
F-box and leucine-rich repeat protein 18 (FBXL18) is an E3 ubiquitin ligase that is reported to be involved in the tumorigenesis of various types of cancer. However, it remains unknown whether FBXL18 is correlated with hepatocarcinogenesis. METHODS AND RESULTS: In the current study, we found that FB...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Lippincott Williams & Wilkins
2023
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10309527/ https://www.ncbi.nlm.nih.gov/pubmed/37378633 http://dx.doi.org/10.1097/HC9.0000000000000198 |
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author | Yu, Hong-Qiang Li, Feng Xiong, HaoJun Fang, Lei Zhang, Jie Bie, Ping Xie, Chuan-Ming |
author_facet | Yu, Hong-Qiang Li, Feng Xiong, HaoJun Fang, Lei Zhang, Jie Bie, Ping Xie, Chuan-Ming |
author_sort | Yu, Hong-Qiang |
collection | PubMed |
description | F-box and leucine-rich repeat protein 18 (FBXL18) is an E3 ubiquitin ligase that is reported to be involved in the tumorigenesis of various types of cancer. However, it remains unknown whether FBXL18 is correlated with hepatocarcinogenesis. METHODS AND RESULTS: In the current study, we found that FBXL18 was highly expressed in HCC tissues and positively associated with poor overall survival of HCC patients. FBXL18 was an independent risk factor for HCC patients. We observed that FBXL18 drove HCC in FBXL18 transgenic mice. Mechanistically, FBXL18 promoted the K63-linked ubiquitination of small-subunit ribosomal protein S15A (RPS15A) and enhanced its stability, increasing SMAD family member 3 (SMAD3) levels and translocation to the nucleus and promoting HCC cell proliferation. Moreover, the knockdown of RPS15A or SMAD3 significantly suppressed FBXL18-mediated HCC proliferation. In clinical samples, elevated FBXL18 expression was positively associated with RPS15A expression. CONCLUSION: FBXL18 promotes RPS15A ubiquitination and upregulates SMAD3 expression, leading to hepatocellular carcinogenesis, and this study provides a novel therapeutic strategy for HCC treatment by targeting the FBXL18/RPS15A/SMAD3 pathway. |
format | Online Article Text |
id | pubmed-10309527 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Lippincott Williams & Wilkins |
record_format | MEDLINE/PubMed |
spelling | pubmed-103095272023-06-30 Elevated FBXL18 promotes RPS15A ubiquitination and SMAD3 activation to drive HCC Yu, Hong-Qiang Li, Feng Xiong, HaoJun Fang, Lei Zhang, Jie Bie, Ping Xie, Chuan-Ming Hepatol Commun Original Article F-box and leucine-rich repeat protein 18 (FBXL18) is an E3 ubiquitin ligase that is reported to be involved in the tumorigenesis of various types of cancer. However, it remains unknown whether FBXL18 is correlated with hepatocarcinogenesis. METHODS AND RESULTS: In the current study, we found that FBXL18 was highly expressed in HCC tissues and positively associated with poor overall survival of HCC patients. FBXL18 was an independent risk factor for HCC patients. We observed that FBXL18 drove HCC in FBXL18 transgenic mice. Mechanistically, FBXL18 promoted the K63-linked ubiquitination of small-subunit ribosomal protein S15A (RPS15A) and enhanced its stability, increasing SMAD family member 3 (SMAD3) levels and translocation to the nucleus and promoting HCC cell proliferation. Moreover, the knockdown of RPS15A or SMAD3 significantly suppressed FBXL18-mediated HCC proliferation. In clinical samples, elevated FBXL18 expression was positively associated with RPS15A expression. CONCLUSION: FBXL18 promotes RPS15A ubiquitination and upregulates SMAD3 expression, leading to hepatocellular carcinogenesis, and this study provides a novel therapeutic strategy for HCC treatment by targeting the FBXL18/RPS15A/SMAD3 pathway. Lippincott Williams & Wilkins 2023-06-28 /pmc/articles/PMC10309527/ /pubmed/37378633 http://dx.doi.org/10.1097/HC9.0000000000000198 Text en Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Association for the Study of Liver Diseases. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License 4.0 (https://creativecommons.org/licenses/by/4.0/) (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) |
spellingShingle | Original Article Yu, Hong-Qiang Li, Feng Xiong, HaoJun Fang, Lei Zhang, Jie Bie, Ping Xie, Chuan-Ming Elevated FBXL18 promotes RPS15A ubiquitination and SMAD3 activation to drive HCC |
title | Elevated FBXL18 promotes RPS15A ubiquitination and SMAD3 activation to drive HCC |
title_full | Elevated FBXL18 promotes RPS15A ubiquitination and SMAD3 activation to drive HCC |
title_fullStr | Elevated FBXL18 promotes RPS15A ubiquitination and SMAD3 activation to drive HCC |
title_full_unstemmed | Elevated FBXL18 promotes RPS15A ubiquitination and SMAD3 activation to drive HCC |
title_short | Elevated FBXL18 promotes RPS15A ubiquitination and SMAD3 activation to drive HCC |
title_sort | elevated fbxl18 promotes rps15a ubiquitination and smad3 activation to drive hcc |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10309527/ https://www.ncbi.nlm.nih.gov/pubmed/37378633 http://dx.doi.org/10.1097/HC9.0000000000000198 |
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